Silymarin protects spinal cord and cortical cells against oxidative stress and lipopolysaccharide stimulation

Abstract

Contusive spinal cord injury (SCI) is a devastating event which leads to a loss of neurological function below the level of injury. A secondary degenerative process is initiated following acute SCI. This secondary cascade provides opportunities for the delivery of therapeutic interventions. Silymarin, a widely used "liver herb", is frequently used for the protection against various hepatobiliary problems. However, the effectiveness of silymarin in central nervous system (CNS), especially in spinal cord, is not firmly established. The present work evaluates the effects of silymarin and its major constituent, silybin, on oxidative stress and lipopolysaccharide (LPS) stimulation in primary neuronal/glial cell cultures and in vivo. Silymarin or silybin inhibited glial cell proliferation in a concentration-dependent manner. Furthermore, it protected glial cells against peroxide-induced reactive oxygen species (ROS) formation, ATP depletion, and cell damage. Interestingly, the inhibition of peroxide-induced ROS by silybin could be partially attenuated by inhibitors of NFκB or protein kinase C (PKC), suggesting an involvement of NFκB and PKC signaling pathways. In mixed neuronal/glial cell cultures from cerebral cortex or spinal cord, silymarin or silybin effectively attenuated peroxide-induced ROS formation, with silymarin being more effective than silybin, implicating other constituents of silymarin that may be involved. Consistently, silymarin reduced LPS-induced injures in spinal neuronal/glial cell cultures. In vivo, intrathecal administration of silymarin immediately after eliciting contusive SCI effectively improved hindlimb locomotor behavior in the rats. Taken together, silymarin or silybin shows promise in protecting the CNS cells from toxin- or injury-induced damages and might be used to treat head- or spinal cord-injuries related to free radical assault.